thromboplastin and Head-and-Neck-Neoplasms

Elevated tissue factor (TF) expression, although restricted in normal tissue, has been reported in multiple solid cancers, and expression has been associated with poor prognosis. This manuscript compares TF expression across various solid tumor types via immunohistochemistry in a single study, which has not been performed previously.. To increase insight in the prevalence and cellular localization of TF expression across solid cancer types, we performed a detailed and systematic analysis of TF expression in tumor tissue obtained from patients with ovarian, esophageal, bladder, cervical, endometrial, pancreatic, prostate, colon, breast, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and glioblastoma. The spatial and temporal variation of TF expression was analyzed over time and upon disease progression in patient-matched biopsies taken at different timepoints. In addition, TF expression in patient-matched primary tumor and metastatic lesions was also analyzed.. TF expression was detected via immunohistochemistry (IHC) using a validated TF-specific antibody. TF was expressed in all cancer types tested, with highest prevalence in pancreatic cancer, cervical cancer, colon cancer, glioblastoma, HNSCC, and NSCLC, and lowest in breast cancer. Staining was predominantly membranous in pancreatic, cervical, and HNSCC, and cytoplasmic in glioblastoma and bladder cancer. In general, expression was consistent between biopsies obtained from the same patient over time, although variability was observed for individual patients. NSCLC biopsies of primary tumor and matched lymph node metastases showed no clear difference in TF expression overall, although individual patient changes were observed.. This study shows that TF is expressed across a broad range of solid cancer types, and expression is present upon tumor dissemination and over the course of treatment.

Topics: Carcinoma, Non-Small-Cell Lung; Female; Glioblastoma; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Squamous Cell Carcinoma of Head and Neck; Thromboplastin

: Microvesicles associated with tissue factor (TF) may play a role in cancer-related venous thromboembolism; however, not much is known about their interaction with the tumour stroma, especially the endothelium or any procoagulant changes seen because of this interaction. Using a head and neck squamous cell carcinoma line (UMSCC81B) and human umbilical vein endothelial cells (HUVECs), this study explored the interaction of cancer microvesicles released into cell culture media with endothelial cells in vitro, and assessed the procoagulant activity resulting from this interaction. Cell-free media containing UMSCC81B cancer microvesicles supported coagulation in a concentration-dependent manner, suggesting TF and microvesicle presence, this media was then added to HUVECs and flow cytometry analysis showed a subpopulation of HUVECs that had acquired a significantly high expression of TF, which was dependent upon the concentration of UMSCC81B media containing microvesicles present and confocal microscopy confirmed HUVECs associated with labelled microvesicles. The range of TF-positive HUVECs was determined to be 0, 4.2(±1.4), 12.5(±3.72), and 45.9(±18.7)% for microvesicle-positive media concentration of 0, 25, 50, and 100%, respectively, which resulted in decreasing prothrombin values of more than 600 (no clot), 126.4, 65.8, and 47.8 s. Our results demonstrate that procoagulant microvesicles shed by UMSCC81B induced a procoagulant effect in HUVECs through increased clotting activity and cell membrane surface expression of TF.

Topics: Blood Coagulation; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell-Derived Microparticles; Endothelial Cells; Endothelium, Vascular; Head and Neck Neoplasms; Human Umbilical Vein Endothelial Cells; Humans; Squamous Cell Carcinoma of Head and Neck; Thromboplastin; Venous Thromboembolism

This study aimed to understand the relationship between tissue factor (TF) and laryngeal carcinoma.. Differences in TF expression between pericarcinomatous and carcinomatous tissues were studied in patients with laryngeal carcinoma; the potential clinical significance of the observed differences is discussed. Immunohistochemical, western blot, and RT-PCR analyses were performed to assess the expression of TF at the protein and mRNA levels, and differences between pericarcinomatous and carcinomatous tissues in patients (n = 20) with laryngeal carcinoma were analyzed.. Expression of TF was significantly higher in pericarcinomatous tissues than in carcinomatous tissues (P < 0.01); furthermore, the intensity of TF mRNA expression was also significantly stronger in pericarcinomatous than in carcinomatous tissue (P < 0.001). Robust expression of TF was observed in pericarcinomatous tissues but not in carcinomatous tissues.. TF may contribute to the carcinogenesis and development of laryngeal carcinoma and may provide a marker for assessment of the degree of malignancy and the progression of laryngeal carcinoma. TF may also provide a new target for therapeutics for human head and neck cancer.

Topics: Adult; Aged; Biomarkers, Tumor; Female; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Male; Middle Aged; Thromboplastin

Generation of thromboplastin by monocytes has been shown to play a vital role in hypercoagulable states seen in malignancy. The purpose of this study was to compare the procoagulant activity in cancer patients and controls. Recalcification times (RT) of whole blood from 19 normal volunteers, 8 patients with benign polyps, 12 patients previously treated by surgery for head and neck (H&N) or colon cancer, and 13 untreated patients with various stages of H&N or colon cancer were determined. Tests were performed with and without stimulation with Escherichia coli endotoxin. The mean RT in saline (RTS) of untreated patients with early cancer (4.58 +/- 0.83 min) and that of patients with advanced cancer (5.23 +/- 1.16 min) were lower than that of controls (6.55 +/- 0.82 min), P less than 0.01 and P less than 0.05, respectively. The RTS of patients previously treated and of those with benign polyps were no different from those of controls. Activation with endotoxin significantly lowered the recalcification times (RTE) in the early (3.90 +/- 0.58 min) and advanced cancer patients (4.23 +/- 0.66 min) compared to the RTE of controls (5.69 +/- 0.75 min, P less than 0.01 for both groups) as well as compared to those with benign tumors, P less than 0.05. The mean RTE of previously treated patients (4.72 +/- 0.58 min) was also lower than that of controls, P less than 0.05. Our results suggest that RT is significantly reduced in cancer patients compared to that of controls. Furthermore, monocyte activation with endotoxin may enable us to distinguish cancer patients from controls as well as from those with benign tumors.

Topics: Adenoma; Adult; Blood Coagulation Tests; Carcinoma, Squamous Cell; Colonic Neoplasms; Head and Neck Neoplasms; Humans; Male; Middle Aged; Monocytes; Neoplasms; Thromboplastin